Carrier nanoparticles and related compositions, methods and systems

Abstract

Carrier nanoparticles comprising a polymer containing a polyol coupled to a polymer containing a boronic acid and a linkage cleavable under reducing conditions, configured to present the polymer containing a boronic acid to an environment external to the nanoparticle and related compositions, methods and systems.

What is claimed is: 
     
       1. A nanoparticle comprising a polymer containing a polyol and a polymer containing a boronic acid, the polymer containing the boronic acid having proximal and distal ends, the proximal end comprising the boronic acid and the distal end comprising a functional group, wherein the polymer containing the boronic acid is conjugated to the polymer containing the polyol with a reversible borate ester linkage, and wherein the nanoparticle is configured to present the polymer containing the boronic acid to an environment external to the nanoparticle,
 wherein the polymer containing a polyol comprises one or more of at least one of the following structural units of Formula (I), (II), or (III): 
 
       
         
           
           
               
               
           
         
       
       wherein:
 A comprises a polyol having 4 or 6 adjacent hydroxyl groups; and 
 B comprises a neutral, cationic, or anionic organic moiety having a chemical backbone comprising —C m H 2m — linkages, where m≥1, and one or more:
 (a) polyglycol linkage, —(CH 2 —CH 2 —O) p —, in the chemical backbone, where p is from 20-200; and/or 
 (b) amidinium, quaternary ammonium, or imidazolium functional group in the chemical backbone; and/or 
 (c) sulfonate, nitrate, carboxylate, phosphonate, or primary or secondary amine bonded to the chemical backbone; and 
 wherein A and B are covalently linked by amide or ester linkages. 
 
 
     
     
       2. The nanoparticle of  claim 1 , wherein A comprises mucic acid. 
     
     
       3. The nanoparticle of  claim 1 , wherein A comprises glucose, fructose, mannitol, sucrose, galactose, sorbitol, xylose or galactose. 
     
     
       4. The nanoparticle of  claim 1 , wherein B comprises a polyglycol linkage, —(CH 2 —CH 2 —O) p —, where p is from 20-200. 
     
     
       5. The nanoparticle of  claim 1 , wherein B comprises an amidinium, quaternary ammonium, or imidazolium functional group in the chemical backbone. 
     
     
       6. The nanoparticle of  claim 1 , wherein B comprises a sulfonate, nitrate, carboxylate, phosphonate, or primary or secondary bonded to the chemical backbone. 
     
     
       7. The nanoparticle of  claim 1 , wherein the boronic acid is a phenyl boronic acid. 
     
     
       8. The nanoparticle of  claim 1 , wherein the polyol containing the boronic acid is: 
       
         
           
           
               
               
           
         
         wherein
 X 1  is —NH—C(═O)—, —S—S—, —C(═O)—NH—, —O—C(═O)— or —C(═O)—O—, 
 t is from 2 to 2000, and 
 Functional group 2 comprises a terminal —B(OH) 2 , —OCH 3 , —COOH, —NH 2 , or —OH group. 
 
       
     
     
       9. The nanoparticle of  claim 8 , wherein t is from 200 to 300. 
     
     
       10. The nanoparticle of  claim 1 , further comprising a targeting ligand bonded to the functional group at the distal end of the boronic acid polymer. 
     
     
       11. The nanoparticle of  claim 10 , wherein the targeting ligand is a ligand for a cellular receptor, a cellular receptor protein, a ligand for a cellular receptor, or cellular receptor protein. 
     
     
       12. The nanoparticle of  claim 10 , wherein the targeting ligand is a vitamin, a protein, a monosaccharide, a peptide, a peptide aptamer, an oligopeptide, a polypeptide or fragment thereof, a polysaccharide, a polynucleotide, an antibody, or an antibody fragment. 
     
     
       13. The nanoparticle of  claim 10 , wherein the targeting ligand agent is transferrin, folic acid, or galactose. 
     
     
       14. The nanoparticle of  claim 1 , further comprising a therapeutic agent. 
     
     
       15. The nanoparticle of  claim 14 , wherein the therapeutic agent is a chemotherapeutic agent. 
     
     
       16. The nanoparticle of  claim 15 , wherein the chemotherapeutic agent is an epothilone, a camptothecin-based drug, taxol, or a nucleic acid, or a combination thereof. 
     
     
       17. The nanoparticle of  claim 15 , wherein the chemotherapeutic agent is camptothecin, an epothilone, a taxane or a combination thereof. 
     
     
       18. The nanoparticle of  claim 16 , wherein the nucleic acid is a plasmid, siRNA, shRNA, miRNA, antisense oligonucleotide, aptamer, or a combination thereof. 
     
     
       19. The nanoparticle of  claim 1 , further comprising:
 (a) a targeting ligand bonded to the functional group at the distal end of the boronic acid polymer, wherein the targeting ligand is a ligand for a cellular receptor, a cellular receptor protein, a ligand for a cellular receptor, or cellular receptor protein; and 
 (b) a therapeutic agent. 
 
     
     
       20. A method of delivering a therapeutic agent to a human patient, to treat a functional disorder in a human patient's body, the method comprising administering to the human patient a plurality of nanoparticles of  claim 19 . 
     
     
       21. The method of  claim 20 , wherein the functional disorder is a mental disorder. 
     
     
       22. The method of  claim 20 , wherein the functional disorder is a physical disorder. 
     
     
       23. The method of  claim 20 , wherein the functional disorder is a cancer and the therapeutic agent is a chemotherapeutic agent.